Description: Homo sapiens intersectin 1 (SH3 domain protein) (ITSN1), transcript variant 1, mRNA. RefSeq Summary (NM_003024): The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr21:35,014,784-35,261,609 Size: 246,826 Total Exon Count: 40 Strand: + Coding Region Position: hg19 chr21:35,091,134-35,260,604 Size: 169,471 Coding Exon Count: 39
ID:ITSN1_HUMAN DESCRIPTION: RecName: Full=Intersectin-1; AltName: Full=SH3 domain-containing protein 1A; AltName: Full=SH3P17; FUNCTION: Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1. SUBUNIT: Interacts with dynamin, CDC42, SNAP25 and SNAP23. Clusters several dynamin in a manner that is regulated by alternative splicing. Interacts with clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31. Interacts with ADAM15. INTERACTION: P60953-1:CDC42; NbExp=2; IntAct=EBI-602041, EBI-3625591; Q9NRI5:DISC1; NbExp=3; IntAct=EBI-602041, EBI-529989; Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-602041, EBI-6094986; SUBCELLULAR LOCATION: Endomembrane system (By similarity). Cell junction, synapse, synaptosome (By similarity). Cell projection, lamellipodium. Membrane, clathrin-coated pit. Note=Colocalizes with SGIP1 at the plasma membrane in structures corresponding most problably to clathrin-coated pits (Probable). TISSUE SPECIFICITY: Isoform 2 is ubiquitous in adult and fetal tissues with high expression in skeletal muscle, heart, spleen, ovary, testis and all fetal tissues tested and low expression in thymus, blood, lung, liver and pancreas. Isoform 1 is expressed almost exclusively in the brain, in all brain regions. Not expressed in the spinal cord. DOMAIN: SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31. DOMAIN: The KLERQ domain binds to SNAP-25 and SNAP-23 (By similarity). SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 DH (DBL-homology) domain. SIMILARITY: Contains 2 EF-hand domains. SIMILARITY: Contains 2 EH domains. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 5 SH3 domains. CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of ISTN1 and ISTN2, and a Dab2 mutant with impaired binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a partially overlapping role of the EH domain- containing proteins (PubMed:22648170). SEQUENCE CAUTION: Sequence=AAC50592.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15811
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005085 guanyl-nucleotide exchange factor activity GO:0005089 Rho guanyl-nucleotide exchange factor activity GO:0005509 calcium ion binding GO:0005515 protein binding GO:0019209 kinase activator activity GO:0032947 protein complex scaffold GO:0046872 metal ion binding GO:0070064 proline-rich region binding
Biological Process: GO:0006897 endocytosis GO:0007186 G-protein coupled receptor signaling pathway GO:0007264 small GTPase mediated signal transduction GO:0016032 viral process GO:0035023 regulation of Rho protein signal transduction GO:0035556 intracellular signal transduction GO:0042327 positive regulation of phosphorylation GO:0043065 positive regulation of apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0048013 ephrin receptor signaling pathway GO:0048488 synaptic vesicle endocytosis GO:0051056 regulation of small GTPase mediated signal transduction GO:0051897 positive regulation of protein kinase B signaling GO:0061024 membrane organization
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